This study is registered with ClinicalTrials

Adverse events in randomly assigned patients during post-induction treatment phasesIntramuscular native Escherichia colil-asparaginase (n=231)Intravenous PEG- asparaginase (n=232)p valueAsparaginase toxicity59 (26%)65 (28%)0·60Pancreatitis, grade ≥222 (10%)27 (12%)0·55Mild/moderate16 (7%)14 (6%)0·71Severe8 (3%)13 (6%)0·37Allergy (all grades)*21 (9%)28 (12%)0·36Grades 1 and 213 (6%)14 (6%)0·99Grades 3 and 46 (3%)14 (6%)0·10Thrombosis or bleeding, grade ≥224 (10%)17 (7%)0·26CNS3 (1%)6 (3%)0·50Non-CNS21 (9%)12 (5%)0·11Infection (bacterial/fungal), grade ≥351 (22%)47 (20%)0·65Hyperbilirubinaemia, grade ≥41 (<1%)2 (<1%)0·995-year cumulative incidence Astemizole grade ≥2 osteonecrosis (95% CI)†9% (6–13)9% (5–13)0·855-year cumulative incidence of grade ≥1 bone fracture (95% CI)†23% (18–28)21% (16–27)0·60Data are secondary xylem n (%) unless otherwise indicated. Toxicity was continually monitored during treatment and was graded using the Common Terminology Criteria for Adverse Events version 3.0.*Two additional patients in the intramuscular E colil-asparaginase group experienced an unknown grade of allergy. These patients were not included in the analysis.†The 5-year cumulative incidence of osteonecrosis and fracture was calculated from the date of randomisation using the competing risk regression package in R and compared with the Gray test, with relapse and death in remission as competing risks.Full-size tableTable optionsView in workspaceDownload as CSV